F. Genet

Troublesome Heterotopic Ossification after Central Nervous System Damage: A Survey of 570 Surgeries

Background Heterotopic ossification (HO) is a frequent complication after central nervous system (CNS) damage but has seldom been studied. We aimed to investigate features of HO for the first time in a large sample and the rate of early recurrence of HO in terms of the time of surgery. Methodology/Principal Findings We retrospectively analyzed data from an anonymous prospective survey of patients undergoing surgery between May 1993 and November 2009 in our institution for troublesome HO related to acquired neurological disease. Demographic and HO characteristics and neurological etiologies were recorded. For 357 consecutive patients, we collected data on 539 first surgeries for HO (129 surgeries for multiple sites). During the follow-up, recurrences requiring another surgery appeared in 31 cases (5.8% [31/539]; 95% confidence interval [CI]: 3.8%–7.8%; 27 patients). Most HO requiring surgery occurred after traumatic brain injury (199 patients [55.7%]), then spinal cord injury (86 [24.0%]), stroke (42 [11.8%]) and cerebral anoxia (30 [8.6%]). The hip was the primary site of HO (328 [60.9%]), then the elbow (115 [21.3%]), knee (77 [14.3%]) and shoulder (19 [3.5%]). For all patients, 181 of the surgeries were performed within the first year after the CNS damage, without recurrence of HO. Recurrence was not associated with etiology (p = 0.46), sex (p = 1.00), age at CNS damage (p = 0.2), multisite localization (p = 0.34), or delay to surgery (p = 0.7). Conclusions/Significance In patients with CNS damage, troublesome HO and recurrence occurs most frequently after traumatic brain injury and appears frequently in the hip and elbow. Early surgery for HO is not a factor of recurrence.

Neurological heterotopic ossification following spinal cord injury is triggered by macrophage-mediated inflammation in muscle.

Neurological heterotopic ossification (NHO) is the abnormal formation of bone in soft tissues as a consequence of spinal cord or traumatic brain injury. NHO causes pain, ankyloses, vascular and nerve compression and delays rehabilitation in this high‐morbidity patient group. The pathological mechanisms leading to NHO remain unknown and consequently there are no therapeutic options to prevent or reduce NHO. Genetically modified mouse models of rare genetic forms of heterotopic ossification (HO) exist, but their relevance to NHO is questionable. Consequently, we developed the first model of spinal cord injury (SCI)‐induced NHO in genetically unmodified mice. Formation of NHO, measured by micro‐computed tomography, required the combination of both SCI and localized muscular inflammation. Our NHO model faithfully reproduced many clinical features of NHO in SCI patients and both human and mouse NHO tissues contained macrophages. Muscle‐derived mesenchymal progenitors underwent osteoblast differentiation in vitro in response to serum from NHO mice without additional exogenous osteogenic stimuli. Substance P was identified as a candidate NHO systemic neuropeptide, as it was significantly elevated in the serum of NHO patients. However, antagonism of substance P receptor in our NHO model only modestly reduced the volume of NHO. In contrast, ablation of phagocytic macrophages with clodronate‐loaded liposomes reduced the size of NHO by 90%, supporting the conclusion that NHO is highly dependent on inflammation and phagocytic macrophages in soft tissues. Overall, we have developed the first clinically relevant model of NHO and demonstrated that a combined insult of neurological injury and soft tissue inflammation drives NHO pathophysiology. Copyright

Referral to Rehabilitation After Severe Traumatic Brain Injury: Results From the PariS-TBI Study

Background. After a severe traumatic brain injury (TBI), some patients are discharged home without rehabilitation, although rehabilitation is assumed to improve outcome. Objective. To assess factors that predict referral to rehabilitation following acute care. This study is part of a larger inception cohort study assessing the care network in the Parisian area (France). Methods. Between July 2005 and April 2007, 504 adults with severe TBI (Glasgow Coma Scale score ≤8) were prospectively recruited by mobile emergency services. This study included 254 acute care survivors (80% male, median age 32 years). Data regarding demographics, injury severity, and acute care pathway were collected. The first analysis compared patients referred to a rehabilitation facility with patients discharged to a living place. The second analysis compared patients referred to a specialized neurorehabilitation (NR) facility with patients referred to nonspecialized rehabilitation. Univariate and multivariate statistics were computed. Results. In all, 162 patients (64%) were referred to rehabilitation, 115 (45%) of which were referred to NR and 47 (19%) to nonspecialized rehabilitation. The following factors were significantly predictive of nonreferral to rehabilitation: living alone, a lower income professional category, pretraumatic alcohol abuse, lower TBI severity, and transfer through a nonspecialized medical ward before discharge. Patients referred to specialized NR were significantly younger and from a higher income professional category. Conclusions. These results raise concern regarding care pathways because many patients were discharged to living places, probably without adequate assessment and management of rehabilitation needs. Injury severity and social characteristics influenced discharge destination.

Manual needle placement: accuracy of botulinum toxin A injections.

Introduction: Electrophysiological or ultrasound guidance can facilitate botulinum toxin A (BoNt‐A) injection accuracy, but clinical landmarks and palpation are often used for superficial muscles. We evaluated the accuracy of manual needle placement in the gastrocnemius muscles (GC) guided only by anatomical landmarks and palpation. Methods: Bilateral limbs from 30 cadavers were used to evaluate ink injection into the GC. One anatomist and one orthopedic surgeon verified the accuracy of manual needle placement postinjection by calf muscle dissection. Injection was considered a failure if the ink was not located in the head of the target GC. Results: One hundred twenty‐one practitioners were evaluated. Fifty‐two injections were successful (43%), and 69 failed (57%). This result was unrelated to injector experience (P = 0.097). Conclusions: Our findings show a poor success rate, regardless of injector experience. Therefore, muscle palpation and anatomical landmarks are insufficient to ensure the accuracy of BoNt‐A injections, even for large, superficial muscles. Muscle Nerve 46: 531–534, 2012

The impact of preoperative hip heterotopic ossification extent on recurrence in patients with head and spinal cord injury: a case control study.

Background The preoperative Heterotopic Ossification (HO) extent is usually one of the main used criteria to predict the recurrence before excision. Brooker et al built a radiologic scale to assess this pre operative extent around the hip. The aim of this study is to investigate the relationship between the recurrence risk after hip HO excision in Traumatic Brain Injury (TBI) and Spinal Cord Injury (SCI) patients and the preoperative extent of HO. Methodology/Principal Findings A case control study including TBI or SCI patients following surgery for troublesome hip HO with (case, n = 19) or without (control, n = 76) recurrence. Matching criteria were: sex, pathology (SCI or TBI) and age at the time of surgery (+/−4.5 years). For each etiology (TBI and SCI), the residual cognitive and functional status (Garland classification), the preoperative extent (Brooker status), the modified radiological and functional status (GCG-BD classification), HO localization, side, mean age at the CNS damage, mean delay for the first HO surgery, and for the case series, the mean operative delay for recurrence after the first surgical intervention were noted. Conclusions/Significance The median delay for first HO surgery was 38.6 months (range 4.5 to 414.5;) for the case subgroup and 17.6 months (range 5.7 to 339.6) for the control group. No significant link was found between recurrence and operative delay (p = 0.51); the location around the joint (0.07); the Brooker (p = 0.52) or GCG-BD status (p = 0.79). Including all the matching factors, no significant relationship was found between the recurrence HO risk and the preoperative extent of troublesome hip HO using Brooker status (OR = 1.56(95% CI: 0.47–5.19)) or GCG-BD status (OR class 3 versus 2 = 0.67(95% CI: 0.11–4.24) and OR class 4 versus 2 = 0.79(95%CI: 0.09–6.91)). Until the pathophysiology of HO development is understood, it will be difficult to create tools which can predict HO recurrence.

Impact of the operative delay and the degree of neurologic sequelae on recurrence of excised heterotopic ossification in patients with traumatic brain injury.

The timing of surgery with regard to recurrence risk after neurologic heterotopic ossification (HO) excision is still debated. This study investigated the association between recurrence risk after HO excision in traumatic brain injury (TBI) patients and (1) the operative delay and (2) the degree of neurologic sequelae (Garland status). A case-control study was performed. Patients who developed troublesome HO requiring surgery after TBI with (case, n = 16) or without recurrence (control, n = 64) were retrospectively included. Other matching criteria were sex and age at the time of surgery (± 4 years). The median delay for first HO surgery was 13.7 months (interquartile range: 9.0–37.1) for the case group and 13.2 months (interquartile range: 7.8–30.0) for the control group. No significant link was found between recurrence and operative delay (P = .54), even after inclusion of all matching factors (P = .53), or Garland status (P = .81). The inclusion of Garland status into the model did not change this result (P = .64). After TBI, no link was found between HO operative delay and recurrence. In spite of a common notion of a relationship between initial severity of TBI and HO development, no link was found between HO recurrence risk and the severity of sequelae.

Flexor Origin Slide for Contracture of Spastic Finger Flexor Muscles A Retrospective Study

BACKGROUND Contracture of the wrist and extrinsic finger flexor and pronator muscles is a common consequence of central nervous system disorders. The proximal release of the extrinsic flexor and pronator muscles was first described by Page and Scaglietti for a Volkmann contracture. The aim of the present study was to assess the amount of increase in extension and the improvements in global hand function that can be expected following this lengthening procedure in patients with central nervous system disorders. METHOD A single-center retrospective review of patients with central nervous system lesions and contractures of the wrist and extrinsic finger flexor and forearm pronator muscles, causing aesthetic, hygienic, or functional impairment, was carried out. The Page-Scaglietti technique was used for all interventions. Before the operation, motor nerve blocks were used to distinguish between spasticity and contractures with surgical intervention only for contractures. The Zancolli and House classifications were used to evaluate improvements. RESULTS Data from fifty-four hands and fifty patients (thirty-five men and fifteen women) were evaluated. The mean duration of follow-up (and standard deviation) was 26 ± 21 months (range, three to 124 months). The mean gain (and standard deviation) in wrist extension with fingers extended was 67° ± 25° (range, -10° to 110°). Preoperatively, no hands were classified as Zancolli Group 1, whereas twenty-five hands were classified as Zancolli Group 1 at the latest follow-up review. Ten nonfunctional hands (rated as House Group 0 or Group 1) became functional as a supporting hand postoperatively. Zancolli and House classifications increased significantly (p < 0.01) postoperatively. In twelve cases, a partial recurrence of the deformity occurred. In seven of these cases, surgery unmasked spasticity or contracture of the intrinsic muscles, which required further intervention. CONCLUSION The Page-Scaglietti technique appears to improve range of motion and function in people with wrist and finger contractures due to central nervous system disorders.

Botulinum Toxin Effect on Voluntary and Stretch Reflex–Related Torque Produced by the Quadriceps An Isokinetic Pilot Study

Background. An understanding of the mechanical effects of botulinum toxin type A (BoNT A) on spastic and voluntary muscle contraction may help predict functional responders. Objective. To compare the effect of BoNT A on the voluntary and stretch reflex–related torques produced by activation of the rectus femoris (RF). Methods. This was a prospective open study where 15 incomplete spinal cord injury patients, impaired by a stiff-knee gait, with RF hyperactivity in mid-swing quantified by formal gait analysis (GA), were assessed before and after RF BoNT A injection (Botox, 200 UI). Main outcome measures included isokinetic peak torque (and angle at peak torque) at 0° (supine) and 90° (seated) during passive stretch (10 deg/s, 90 deg/s, and 150 deg/s), and voluntary contraction (60 deg/s) of the quadriceps. Secondary measures included impairment by Modified Tardieu Scale (MTS), peak knee flexion and spatial-temporal data by GA, activity (6-minute walking test, timed stair climbing), and discomfort (Verbal Rating Scale). Results. Voluntary torque decreased (−16%; P = .0004) but with only a trend toward a decrease in stretch reflex–related torque. The angle at spastic torque increased at 90 deg/s (+5°; P = .03), whereas MTS, peak knee flexion (+4°; P = .01), spatial-temporal data, timed stair climbing test (25%; P = .02), and discomfort were significantly improved. Conclusion. BoNT A appeared to delay the stretch-reflex angle at peak torque, whereas the voluntary torque decreased. After strict patient selection, BoNT A injection into the RF muscle led to improvements in impairment, activity, and discomfort.

Pilot study evaluating the safety of intradetrusor injections of botulinum toxin type a: Investigation of generalized spread using single-fiber EMG†‡§

Intradetrusor botulinum toxin type‐A injections are a novel therapy for treatment of neurogenic overactive bladder resistant to parasympatholytic treatment. In rare cases, however, it may be associated with generalized muscle weakness. Single‐fiber electromyographic (SFEMG) analysis of neuromuscular jitter (NJ) was used to study OnabotulinumtoxinA (BOTOX®) migration to striated muscle.

Single-Fiber Electromyography Analysis of Botulinum Toxin Diffusion in Patients With Fatigue and Pseudobotulism

OBJECTIVE To characterize electromyographic abnormalities according to symptoms (asymptomatic, fatigue, pseudobotulism) reported 1 month after botulinum toxin injection. DESIGN Retrospective, single-center study comparing single-fiber electromyography (SFEMG) in the extensor digitorum communis (EDC) or orbicularis oculi (OO) muscles. SETTING Hospital. PARTICIPANTS Four groups of adults treated for spasticity or neurologic bladder hyperactivity (N=55): control group (asymptomatic patients: n=17), fatigue group (unusual fatigue with no weakness: n=15), pseudobotulism group (muscle weakness and/or visual disturbance: n=20), and botulism group (from intensive care unit of the same hospital: n=3). INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Mean jitter, percentage of pathologic fibers, and percentage of blocked fibers were compared between groups. RESULTS SFEMG was abnormal for 17.6% of control patients and 75% of patients in the pseudobotulism group. There were no differences between the control and fatigue groups. Mean jitter, percentage of pathologic fibers, and percentage of blocked fibers of the EDC muscle were significantly higher in the pseudobotulism group than in the fatigue and control groups. There were no differences between groups for the OO muscle. The SFEMG results in the botulism group were qualitatively similar to those of the pseudobotulism group. CONCLUSIONS SFEMG of the EDC muscle confirmed diffusion of the toxin into muscles distant from the injection site in the pseudobotulism group. SFEMG in the OO muscle is not useful for the diagnosis of diffusion. No major signs of diffusion of botulinum toxin type A were found away from the injection site in patients with fatigue but no motor weakness. Such fatigue may be related to other mechanisms.